In this specification, the term "amino acids" denotes amino acids and their derivatives; while "N-carboxylic anhydrides" and "N-carboxylic anhydrides of amino acids" are referred to as "NCA" and "ANCA", respectively; and "trichloromethylchloroformate", i.e., (CCl.sub.3 OCOCl) is referred to as "TCF".
It is known to prepare ANCA by suspending an amino acid or its salt in an organic solvent, reacting the suspension with phosgene blown thereinto at an elevated temperature of about from 40.degree. to 100.degree.C and cooling the reaction mixture to effect crystallization of the ANCA. However, the use of phosgene, which is poisonous gas is quite dangerous. Furthermore, because the boiling point of phosgene is 8.2.degree.C (measured at 760 mmHg), there is a great probability that phosgene blown into the reaction system is liable to escape therefrom.
The reaction for preparing ANCA from amino acid and phosgene is considered to proceed in the following manner: ##EQU1## wherein R is an amino acid radical. [Advance in Protein Chemistry, Vol. 3, page 268 (1958), Academic Press Inc. Publisher, New York, N.Y.]
In these series of reactions, the latter reaction proceeds faster than the former, i.e., one third of the amino acid in the starting mixture is quickly converted into ANCA; while the remaining two thirds of the amino acid is considered to be readily converted into the hydrochloride thereof represented by ##EQU2## BY THE ACTION OF THE BY-PRODUCT HYDROGEN CHLORIDE. The reaction for obtaining ANCA from amino acid and phosgene proceeds with a high velocity, while the velocity of the reaction between the hydrochloride of amino acid and phosgene is relatively slow. The reaction velocity of dehydrogenchloride to give NCA is accelerated by elevating the reaction temperature. However, when the temperature of the reaction system is elevated, the concentration of the phosgene dissolved in the reaction solvent reduces, resulting in slow reaction velocity to NCA. It is necessary for acceleration of the reaction velocity to dissolve a largest possible amount of phosgene in the solvent at an elevated reaction temperature. However, the use of a large amount of solvent for this purpose is very disadvantageous in industrial practice; and even if such a large amount of solvent is used, it is usually necessary to use more than 2-3 mols of phosgene per mol of the amino acid or its salt, utilized in the reaction.
In order to increase the solubility of phosgene in the solvent and/or to accelerate the reaction valocity, various attempts such as acceleration of agitation and improvement of gas-charging devices, etc. have been made. However, because of the very corrosive nature of both phosgene and hydrogen chloride which is given off during the reaction, it is difficult to achieve the desired purposes.
It has now unexpectedly been discovered that the reaction for preparing ANCA from amino acids can be carried out by using TCF in place of phosgene, which is a health hazard.
It is therefore an object of the present invention to provide a process for preparing ANCA from amino acids and salts thereof in a simple manner and without any deleterious influence upon human health.
Another object of the present invention is to provide a process for preparing ANCA having a higher quality.
It is another object of the invention to provide a process for preparing ANCA by reaction of amino acids with TCF.